Prognostic significance of HIF-1α polymorphisms in transitional cell carcinoma of the bladder
Version of Record online: 13 NOV 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 122, Issue 6, pages 1297–1302, 15 March 2008
How to Cite
Nadaoka, J., Horikawa, Y., Saito, M., Kumazawa, T., Inoue, T., Narita, S., Yuasa, T., Satoh, S., Nishiyama, H., Ogawa, O., Tsuchiya, N. and Habuchi, T. (2008), Prognostic significance of HIF-1α polymorphisms in transitional cell carcinoma of the bladder. Int. J. Cancer, 122: 1297–1302. doi: 10.1002/ijc.23256
- Issue online: 21 JAN 2008
- Version of Record online: 13 NOV 2007
- Manuscript Accepted: 21 SEP 2007
- Manuscript Received: 13 JUL 2007
- Japan Society for Promotion of Science, Japan. Grant Numbers: 19390411, 19591832, 19591833, 19659406
- transitional cell carcinoma, bladder
Recently, two single nucleotide polymorphisms in the hypoxia-inducible factor-1α (HIF-1α) gene, P582S and A588T, were shown to cause significantly higher transcriptional activity than the wild type. We investigated the association between the HIF-1α polymorphisms and the incidence and progression of transitional cell carcinoma of the bladder, and the relationship between the polymorphisms and the tissue vascular endothelial growth factor (VEGF) level or microvessel density (MVD). A total of 219 patients with bladder cancer and 464 healthy native Japanese control subjects were enrolled. Tissue VEGF and HIF-1α expression levels and the mean MVD were evaluated in 73 radical cystectomy specimens by immunohistochemistry. The HIF-1α genotype did not significantly influence the incidence or disease status of bladder cancer. Among patients who underwent radical cystectomy, those with a variant allele had significantly worse disease-free survival (p = 0.001) and disease-specific survival (p = 0.006) than those without a variant allele. Multivariate analysis using a Cox proportional hazard model revealed that the presence of a variant allele was an independent predictor of disease-free survival (HR = 3.10, 95%CI = 1.38–6.99, p = 0.006). Although not statistically significant, the moderate/high expression levels of VEGF in tumor tissues were more frequently observed in patients with a HIF-1α variant allele (11/13, 84.6%) than in those without (33/60, 55%, p = 0.063). The HIF-1α polymorphisms may have a significant influence on the poor prognosis of the patients undergoing radical cystectomy for bladder cancer, while they seem to have no relation to the bladder cancer occurrence. © 2007 Wiley-Liss, Inc.